开发和验证一种LC-MS/MS方法,用于在人类脑脊液中对贝克西沙林的定量估计
Raja Reddy Kallem1, Rosa Chan1, Katie Neal2
1Department of Clinical Pharmacology and Pharmacometrics, Lundbeck Pharmaceuticals LLC, Deerfield, Illinois, USA.
Biomedical chromatography : BMC
|February 4, 2026
概括
一种经过验证的LC-MS/MS方法量化了人脑脊髓液中的贝克西沙林,用于治疗发育性和性脑病变. 这种方法可确保在临床研究中准确测量贝克西沙林.
科学领域:
- 药理学和毒理学 药理学和毒理学
- 分析化学 分析化学
- 神经科学是一个神经科学.
背景情况:
- 贝克西卡塞林是一种正在研究中的5-基二胺2C (5HT2c) 受体超激活剂.
- 它正在进行与发育性和性脑病变 (DEE) 相关的发作的第三阶段试验.
- 人类脑脊液 (CSF) 的准确量化对于临床评估至关重要.
研究的目的:
- 开发和验证一个简单而强大的LC-MS/MS方法.
- 准确量化人类脑脊液中贝克西沙的度.
- 为了支持贝克西沙林治疗DEE的临床开发.
主要方法:
- 使用了液体染色学-并联质谱法 (LC-MS/MS).
- 样品的制备包括从25μL的人类脑脊液中用同位素标记的内部标准 (13CD2-bexicaserin) 进行稀释提取.
- 在Acquity HSS T3 C18列上进行了染色分离,其梯度为5.5分钟.
主要成果:
- 该方法在0.1-100 ng/mL范围内证明了线性.
- 日内和日间精度在6.3%-8.8%之间,偏差在-15.1%至12.0%之间.
- 在各种条件下证实了贝克西沙林的稳定性,包括板上,自动采样器,冷藏提取物,冷解周期和长期储存.
结论:
- 建立了一种完全验证的LC-MS/MS方法,用于在人类脊髓中量化贝克西沙林.
- 该方法适用于支持bexicaserin的第三阶段临床研究.
- 经过验证的试验提供了可靠的测量,对于评估德患者的贝克西沙林有效性和安全性至关重要.
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